- An umpolung oxa-[2,3] sigmatropic rearrangement employing arynes for the synthesis of functionalized enol ethers
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An oxa-[2,3] sigmatropic rearrangement involving arynes is reported featuring the umpolung of ketones, where the C=O bond polarity is reversed. The in situ-generated sulfur ylides from β-keto thioethers and arynes undergo efficient rearrangement allowing the facile and robust synthesis of functionalized enol ethers in high yields and excellent functional group compatibility. Preliminary mechanistic studies rule out the possibility of Pummerer-type rearrangement operating in this case.
- Gaykar, Rahul N.,George, Malini,Guin, Avishek,Bhattacharjee, Subrata,Biju, Akkattu T.
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supporting information
p. 3447 - 3452
(2021/05/04)
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- Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer
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The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is one of the more recently identified mammalian sources of H2S. A recent study identified several novel 3-MST inhibitors with micromolar potency. Among those, (2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one) or HMPSNE was found to be the most potent and selective. We now took the central core of this compound and modified the pyrimidone and the arylketone sides independently. A 63-compound library was synthesized; compounds were tested for H2S generation from recombinant 3-MST in vitro. Active compounds were subsequently tested to elucidate their potency and selectivity. Computer modeling studies have delineated some of the key structural features necessary for binding to the 3-MST's active site. Six novel 3-MST inhibitors were tested in cell-based assays: they exerted inhibitory effects in murine MC38 and CT26 colon cancer cell proliferation; the antiproliferative effect of the compound with the highest potency and best cell-based activity (1b) was also confirmed on the growth of MC38 tumors in mice.
- Bantzi, Marina,Augsburger, Fiona,Loup, Jérémie,Berset, Yan,Vasilakaki, Sofia,Myrianthopoulos, Vassilios,Mikros, Emmanuel,Szabo, Csaba,Bochet, Christian G.
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p. 6221 - 6240
(2021/05/06)
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- Nucleus-independent chemical shift (NICS) as a criterion for the design of new antifungal benzofuranones
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The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p –1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 μg·mL–1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.
- González-Chávez, Marco Martín,González-Chávez, Rodolfo,Méndez, Francisco,Martínez, Roberto,Ni?o-Moreno, Perla Del Carmen,Ojeda-Fuentes, Luis Enrique,Richaud, Arlette,Zerme?o-Macías, María de los ángeles
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- Photoregulation of Gene Expression with Amantadine-Modified Caged siRNAs through Host–Guest Interactions
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RNA interference is an essential and powerful tool for targeting and verifying specific gene functions. Conditional control of small interfering RNA (siRNA) activity, especially using light activation, is a potential method for regulating target gene expr
- Zhang, Jinhao,Jing, Nannan,Fan, Xinli,Tang, Xinjing
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supporting information
p. 14002 - 14010
(2020/10/02)
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- A photoactivatable microRNA probe for identification of microRNA targets and light-controlled suppression of microRNA target expression
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Here, we report a novel dual-functional microRNA (miRNA) probe, PA-miRNA, for miRNA target identification and light control of miRNA target expression. PA-miRNA is a miRNA mimic with a 3′-biotin tag linked via a photo-cleavable linker. Using PA-miR-34a, i
- Chen, Lei,Li, Jinbo,Sun, Yu.,Zhang, Yan
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supporting information
p. 627 - 630
(2020/01/29)
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- PdCl2/CuCl2/Bi(OTf)3-promoted Construction of Sulfonyl Dibenzooxabicyclo[3.3.1]nonanes and Arylnaphthalenes via Intramolecular Annulation of Sulfonyl o-Allylarylchromanones
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PdCl2/CuCl2/Bi(OTf)3-promoted intramolecular domino annulation of sulfonyl o-allylarylchromanones provides tetracyclic sulfonyl dibenzooxabicyclo[3.3.1]nonanes and bicyclic arylnaphthalenes with good to excellent yields in MeOH at room (25 °C) and refluxing (65 °C) temperature, respectively. The starting sulfonyl o-allylarylchromanones can be easily obtained from the intermolecular cyclocondensation of α-sulfonyl o-hydroxyacetophenones and o-allylbenzaldehydes. The uses of various catalysts and solvent systems are investigated herein for convenient transformation. A plausible mechanism is proposed and discussed. This protocol provides one-pot ring closure via carbon-carbon (C?C) bond formation. (Figure presented.).
- Chang, Meng-Yang,Hsueh, Nai-Chen
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p. 5736 - 5750
(2020/12/01)
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- Synthesis and anti-inflammatory activity of 1,2-3-substituted 2a1,4,5-triazacyclopenta[cd]indene derivatives
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The present study reports the synthesis of 1,2-3-substituted-2a1,4,5-triazacyclopenta[cd]indene derivatives. The synthetic methodology includes some of the prominent reaction steps as specified in sequence (i) Bromination of acetophenones (ii) Condensation of 2-bromo-1-(substituted phenyl) ethanone derivatives with 2-aminopyrimidine, and (iii) Coupling of imidazo[1,2-a]pyrimidine derivatives with 1,2-diaryl/diaklylethynes. The structures of the newly synthesized derivatives have been determined by 1H NMR, 13C NMR, LC-MS, and IR spectral analysis. Furthermore, these derivatives were screened for their preliminary anti-inflammatory activities using Carrageenan induced paw edema test method. These promising screening results suggested a huge potential for the molecular diversity from present compounds that can be inflated to better lead candidates.
- Sanivarapu, Sumalatha,Vaddiraju, Namratha,Velide, Lakshmi
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p. 1461 - 1470
(2019/07/05)
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- α-Ketothioamide Derivatives: A Promising Tool to Interrogate Phosphoglycerate Dehydrogenase (PHGDH)
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Given the putative role of PHGDH in cancer, development of inhibitors is required to explore its function. In this context, we established and validated a straightforward enzymatic assay suitable for high-throughput screening and we identified inhibitors with similar chemical scaffolds. Through a convergent pharmacophore approach, we synthesized α-ketothioamides that exhibit interesting in vitro PHGDH inhibition and encouraging cellular results. These novel probes may be used to understand the emerging biology of this metabolic target.
- Ravez, Séverine,Corbet, Cyril,Spillier, Quentin,Dutu, Alice,Robin, Anita D.,Mullarky, Edouard,Cantley, Lewis C.,Feron, Olivier,Frédérick, Rapha?l
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supporting information
p. 1591 - 1597
(2017/03/08)
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- One-pot synthesis of α-bromo- and α-azidoketones from olefins by catalytic oxidation with in situ-generated modified IBX as the key reaction
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Simple one-pot protocols for the syntheses of α-bromoketones and α-azidoketones starting from olefins have been developed by employing catalytic oxidation of the intermediary bromohydrins with in situ-generated modified IBX as the key reaction. The improved procedure involves initial formation of bromohydrin by the reaction of olefin with NBS in acetonitrile-water mixture (1:1) at rt followed by oxidation with in situ-generated 3,4,5,6-tetramethyl-2-iodoxybenzoic acid (TetMe-IBX), produced in catalytic amounts from 3,4,5,6-tetramethyl-2-iodobenzoic and Oxone. α-Bromoketones are further converted in the same pot to the corresponding α-azidoketones using NaN3/NaHCO3. The one-pot conversions are versatile for a variety of olefins that include cyclic as well as acyclic aliphatic olefins and electron-rich and electron-deficient styrenes. Chemoselective bromohydroxylation of electron-rich double bond and subsequent oxidation to the α-bromoketone is demonstrated for a substrate that contains both electron-rich and deficient double bonds.
- Chandra, Ajeet,Parida, Keshaba Nanda,Moorthy, Jarugu Narasimha
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p. 5827 - 5832
(2017/09/09)
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- Photochemical regulation of gene expression using caged siRNAs with single terminal Vitamin E modification
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Caged siRNAs with a single photolabile linker and/or vitamin E (vitE) modification at the 5′ terminal were rationally designed and synthesized. These virtually inactive caged siRNAs were successfully used to photoregulate both firefly luciferase and GFP g
- Ji, Yuzhuo,Yang, Jiali,Wu, Li,Yu, Lijia,Tang, Xinjing
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supporting information
p. 2152 - 2156
(2016/02/18)
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- Synthesis and antimicrobial activity evaluation of new dithiocarbamate derivatives bearing thiazole/benzothiazole rings
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The synthesis of 2-(substituted phenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A1-A24) derivatives and 2-(4-substituted thiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B1-B14) derivatives was undertaken starting from the potassium salt of 4-(2-pyrimidinyl)piperazine dithiocarbamate. The structures of the obtained compounds were elucidated by1H NMR,13C NMR, MS spectral data, and elemental analysis. The antimicrobial activity of the thirty eight newly synthesized compounds were tested against 12 microorganism strains using the microdilution technique. Compounds 2-(4-ethoxycarbonylthiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B12), 2-(3-fluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A18) and 2-(3,4-difluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A21) were determined to possess high antimicrobial activity.
- Yurtta?, Leyla,?zkay, Yusuf,Duran, Murat,Turan-Zitouni, Gülhan,?zdemir, Ahmet,Cantürk, Zerrin,Kü?üko?lu, Kaan,Kaplanc?kl?, Zafer As?m
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p. 1166 - 1173
(2016/07/27)
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- 1,3-Dibromo-5,5-dimethylhydantoin (DBH) mediated one-pot syntheses of α-bromo/amino ketones from alkenes in water
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α-Bromo ketones are versatile intermediates of high practical utility. Traditional approaches to these compounds are restricted to a relatively hazardous/complex reagent combination, a long reaction time, the use of non-environmentally friendly solvents, or a limited substrate scope. Herein, we describe the development of a new methodology for the preparation of α-bromo ketones from alkenes using 1,3-dibromo-5,5-dimethylhydantoin (DBH) as a bromine source and an oxidant simultaneously. This easy to carry out two-step one-pot protocol proceeds in water and provides high yield of a great variety of α-bromo ketones. Addition of an amine to the intermediate α-bromo ketone further enables the preparation of α-amino ketones in a one-pot sequence.
- Xu, Senhan,Wu, Ping,Zhang, Wei
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p. 11389 - 11395
(2016/12/18)
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- Preparation of precursors for the synthesis of analogues of rhazinilam
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Rhazinilam a structurally relatively simple tetracyclic natural product exerts interesting anticancer activities in vitro, which are difficult to reproduce in vivo. Based on the findings accumulated during the synthetic efforts and on the known metabolic
- Kholod, Inga,Vallat, Olivier,Buciumas, Ana-Maria,Neier, Reinhard
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p. 256 - 273
(2014/05/20)
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- Synthetic strategies for the synthesis and transformation of substituted pyrrolinones as advanced intermediates for rhazinilam analogues
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The biaryl core structure of rhazinilam with its fixed dihedral angle is a pivotal element for its unique in vitro cytotoxic activity. Most of the related natural products are oxidized versions of rhazinilam. Replacing the sensitive pyrrole ring by a pyrrolinone ring is the basis of our initial strategy towards rhazinilam analogues. With this goal, variants of the sequence crossed Mukaiyama aldol reaction followed by the Staudinger reaction were studied. Reacting a suitably substituted acetophenone with O-methyl O-trimethylsilyl ketene acetal gave pyrrolinones 8a and 8b in good to excellent yields. These intermediates could be transformed in four high-yielding steps into the pyrrolic precursors 7a-c containing all the atoms necessary for the construction of rings A, B, and C of rhazinilam. Our studies illustrate a lack of stability of these intermediates. Alternative synthetic approaches towards this central biaryl core structure are described.
- Kholod, Inga,Vallat, Olivier,Buciumas, Ana-Maria,Neels, Antonia,Neier, Reinhard
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supporting information
p. 7865 - 7877
(2015/03/04)
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- Manganese(III) acetate-mediated oxidative cyclization of α-methylstyrene and trans-stilbene with β-ketosulfones
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A convenient microwave irradiation protocol was utilized for the synthesis of β-ketosulfones 1-5 in good yields. These sulfones reacted with alkenes through a radical oxidative cyclization mediated by Mn(OAc)3. Dihydrofurans 6-10 were obtained
- Bouhlel, Ahlem,Curti, Christophe,Tabele, Clemence,Vanelle, Patrice
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p. 4293 - 4307
(2013/06/04)
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- Photocaging strategy for functionalisation of oligonucleotides and its applications for oligonucleotide labelling and cyclisation
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We have used a photocaging strategy to develop novel phosphoramidites and expand the repertoire of protecting groups for modification of oligonucleotides by solid-phase synthesis. We synthesised five photolabile phosphoramidites and four new photolabile c
- Su, Meng,Wang, Jie,Tang, Xinjing
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scheme or table
p. 9628 - 9637
(2012/09/21)
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- Solid-phase synthesis of C-terminal peptide libraries for studying the specificity of enzymatic protein prenylation
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Prenylation is an essential post-translational modification in all eukaryotes. Here we describe the synthesis of a 340-member library of peptides containing free C-termini on cellulose membranes. The resulting library was then used to probe the specificit
- Wang, Yen-Chih,Distefano, Mark D.
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supporting information; experimental part
p. 8228 - 8230
(2012/09/22)
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- Synthesis and rearrangement of 2-(N-Methyl-N-nitroamino)-4-phenylthiazole
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2-(N-Methyl-N-nitroamino)-4-phenylthiazole (5) was prepared and rearranged in aqueous dioxane under influence of sulphuric acid of various concentrations. 2-(N-Methylamino)-5-nitro-4-phenylthiazole (6) was the only product up to 50% acid concentration. At higher acidities, significant amounts of nitro derivatives 3b and 3c, substituted in benzene ring, were also formed. The result indicates that migration of the N-nitro group occurs on the intramolecular path, however, in concentrated sulphuric acid, formation of nitronium ion and ring nitration also takes place.
- Spaleniak,Daszkiewicz,Kyziol
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p. 171 - 178
(2008/02/10)
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- Sodium nitrite-catalyzed oxybromination of aromatic compounds and aryl ketones with a combination of hydrobromic acid and molecular oxygen under mild conditions
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A novel and efficient catalytic system for the oxybromination of aromatic compounds and aryl ketones utilizing a combination of aqueous hydrobromic acid and molecular oxygen in the presence of sodium nitrite under mild conditions has been developed. The newly developed catalytic system utilizes cheap and readily available reactants, exhibits high bromine atom economy and releases only innocuous water as the by-product.
- Zhang, Guofu,Liu, Renhua,Xu, Qing,Ma, Lixin,Liang, Xinmiao
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p. 862 - 866
(2007/10/03)
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- Scavenger assisted combinatorial process for preparing libraries of tertiary amine compounds
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This invention relates to a novel solution phase process for the preparation of tertiary amine combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Dihydropyridines bearing an imidazo[2,1-b]thiazole system
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This paper reports the synthesis of imidazo[2,1-b]thiazoles, bearing a dihydropyridine ring at the 5 or 6 position, which were tested for antiarrhythmic, inotropic and chronotropic activities. Nine of the ten compounds bearing double bond at the 2,3 posit
- Andreani,Leoni,Rambaldi,Locatelli,Bossa,Galatulas,Chiericozzi,Bissoli
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p. 151 - 157
(2007/10/03)
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- Synthesis and biological properties of a new series of anti-MRSA β-Lactams; 2-(thiazol-2-ylthio)carbapenems
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A series of 1β-methylcarbapenems containing variously C-2 substituted thiazol-2-ylthio groups were synthesized, and their in vitro anti-MRSA activity was examined. Among them, 1β-methyl-2-(4-arylthiazol-2-ylthio) carbapenems exhibited superior anti-MRSA activity. Introduction of a cationic moiety in the C-2 side chain not only reduced the binding to HSA but also increased the stability against DHP-I, without affecting the anti-MRSA activity. It was also found that the distance between the cationic moiety and the carbapenem skeleton was related to the strength of HSA binding and the stability against DHP-I.
- Shinagawa, Hisatoshi,Yamaga, Hiroshi,Houchigai, Hitoshi,Sumita, Yoshihiro,Sunagawa, Makoto
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p. 601 - 621
(2007/10/03)
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- Studies on Cerebral Protective Agents. VIII. Synthesis of 2-Aminothiazoles and 2-Thiazolecarboxamides with Anti-anoxic Activity
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Various 2-aminothiazoles (2a-s and 3a-g) and 2-thiazolecarboxamides (4a-h), possessing a nitrogeneous basic moiety at the C-2 position of the thiazole ring, were prepared and tested for anti-anoxic (AA) activity in mice.Among them, N-4-(3-trifluoromethylphenyl)-2-thiazolecarbaxamide hydrochloride (4e, FR108143) (minimum effective doses of 3,2 mg/kg i.p. and 10 mg/kg p.o., respectively) exhibited more potent AA activity than either FK360 or compound 1, each of which has a nitrogeneous basic moiety at the C-5 position.The structure-activity relationship with regard to AA activity of this series of compounds are discussed, and the three-dimensional electrostatic potentials (3D-MEP) around the basic nitrogen atom of FK360 and the thiazole derivative (4e) are compared.Key words cerebral protective agent; anti-anoxia; 2-aminothiazole; 2-thiazolecarboxamide; structure-activity relationship; FK360
- Okhubo, Mitsuru,Kuno, Atsushi,Nakanishi,Isao,Takasugi, Hisashi
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p. 1497 - 1504
(2007/10/03)
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- Synthesis and antibacterial activity of some imidazo[1,2-a[pyrimidine derivatives
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A series of 75 imidazo[1,2-a]pyrimidine derivatives were synthesized. The 'in vitro' antibacterial activity of these compounds and their corresponding α-bromoketones against a variety of gram (+), gram (-) bacteria and Mycobacterium species is reported. Some of the prepared derivatives exhibited potent antimicrobial activity.
- Rival,Grassy,Michel
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p. 1170 - 1176
(2007/10/02)
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- Antibacterial monic acid derivatives
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A compound of the formula (I) STR1 wherein R is a group STR2 R1 is hydrogen, phenyl, C1-20 alkyl, C2-8 alkenyl or C2-8 alkynyl each of which may optionally be substituted; or C3-7 cycloalkyl, X is a divalent group --Y--C=C--, and Y is oxygen or sulphur, have antibacterial and/or antimycoplasmal activity.
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- Imidazopyridazines. VII. Syntheses and Central Nervous System Activities of Some 3-Alkoxy-6-benzyloxy(and methoxybenzyloxy)-2-phenyl(substituted phenyl or pyridinyl)imidazopyridazines
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A series of 15 3-alkoxy-6-benzyloxy(methoxybenzyloxy)-2-phenyl(substituted phenyl and pyridinyl)imidazopyridazines has been prepared and each compound tested for its ability to displace 3H-diazepam from rat brain plasma membranes.The results have b
- Barlin, Gordon B.,Davies, Les P.,Ngu, Maria M. L.
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p. 1749 - 1757
(2007/10/02)
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- Antibacterial Benzisoxazolones. An Unusual Rearrangement Product from o-Nitrostyrene Oxide en Route to the Photolabile Carbonyl Protecting Group (o-Nitrophenyl)ethylene Glycol
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In the process of synthesizing the known, photolabile protecting group (o-nitrophenyl)ethylene glycol, we uncovered an acid-mediated rearrangement of o-nitrostyrene oxide to 1-(hydroxymethyl)-2,1-benzisoxazol-3(1H)-one.The structure was ascertained by IR, UV, 1H NMR, 13C NMR, MS, and X-ray crystallography.Also the benzisoxazolone was prepared by independent synthesis from an o-nitrobenzoate.Another novel transformation uncovered was the conversion of o-nitrostyrene oxide to 2-(o-nitrophenyl)ethanol with use of potassium hydroxide and 18-crown-6.Similiar chemistry was insignificant with p-nitrostyrene oxide.The benzisoxazolone exhibited antibacterial and antileukemic activity (in vitro).
- Wierenga, Wendell,Harrison, Allen W.,Evans, Bruce R.,Chidester, Connie G.
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p. 438 - 442
(2007/10/02)
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- o-Nitrophenylethylene glycol as photoremovable protective group for aldehydes and ketones: syntheses, scope, and limitations
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The preparation of o-nitophenylethylene glycol is described along with its application as a photolabile protective group for aldehydes and ketones.Formation of the acetals and ketals is achieved in good to high yields in the usual manner and deprotection is carried out in fair to high yield, by photolysis at 350 nm in an inert solvent such as benzene.Because of the particular nature of the present protective group, its stability to basic and acidic conditions has been examined and is reported to complete the scope and limitations aspect.From a mechanistic point of view, the isolation and characterisation of o-nitroso-α-hydroxyacetophenone as the spent reagent demonstrates a mechanistic link with the known o-nitrobenzaeldehyde to o-nitrobenzoic acid photorearrangement.
- Gravel, D.,Herbert, J.,Thoraval, D.
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p. 400 - 410
(2007/10/02)
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